Arno Motulsky
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Arno Gunther Motulsky (5 July 1923 – 17 January 2018) was a professor of medical genetics and genome sciences at the
University of Washington The University of Washington (UW and informally U-Dub or U Dub) is a public research university in Seattle, Washington, United States. Founded in 1861, the University of Washington is one of the oldest universities on the West Coast of the Uni ...
. Motulsky is considered a founder of the field of medical genetics. He is also considered the "father of
pharmacogenetics Pharmacogenomics, often abbreviated "PGx," is the study of the role of the genome in drug response. Its name ('' pharmaco-'' + ''genomics'') reflects its combining of pharmacology and genomics. Pharmacogenomics analyzes how the genetic makeup o ...
", and is credited with coining the term. /sup>


Early life

Arno Motulsky was born in
Fischhausen Primorsk (; ; ; ) is a town in Baltiysky District of Kaliningrad Oblast, Russia, located on the Vistula Lagoon. Its population is compared to . Geography The town is located in the southwest of the Sambia Peninsula. It is situated by a bay on ...
near
Königsberg Königsberg (; ; ; ; ; ; , ) is the historic Germany, German and Prussian name of the city now called Kaliningrad, Russia. The city was founded in 1255 on the site of the small Old Prussians, Old Prussian settlement ''Twangste'' by the Teuton ...
,
East Prussia East Prussia was a Provinces of Prussia, province of the Kingdom of Prussia from 1772 to 1829 and again from 1878 (with the Kingdom itself being part of the German Empire from 1871); following World War I it formed part of the Weimar Republic's ...
to German-Jewish parents, Hermann and Rena (Sass) Motulsky. As the
Nazis Nazism (), formally named National Socialism (NS; , ), is the far-right politics, far-right Totalitarianism, totalitarian socio-political ideology and practices associated with Adolf Hitler and the Nazi Party (NSDAP) in Germany. During H ...
consolidated power and adopted
antisemitic Antisemitism or Jew-hatred is hostility to, prejudice towards, or discrimination against Jews. A person who harbours it is called an antisemite. Whether antisemitism is considered a form of racism depends on the school of thought. Antisemi ...
laws, Arno's father Hermann, a merchant, attempted to resist. Offended by the public display in the town square of
Der Stürmer ''Der Stürmer'' (; literally, "The Stormer / Stormtrooper / Attacker") was a weekly German tabloid-format newspaper published from 1923 to the end of World War II by Julius Streicher, the '' Gauleiter'' of Franconia, with brief suspension ...
, the virulently antisemitic pro-Nazi newspaper, he forged a letter to the local Nazi Party branch directing them to remove the Stürmer display boxes. The police traced the letter to him and he served time in prison for his dissidence. Hermann was later pressured by the mayor of Fischhausen to sell his store and other property at undervalued prices to an “Aryan” buyer. The family relocated to Hamburg, living off savings as they explored how and when to emigrate. In June 1938, Hermann was arrested again as part of the Juni-Aktion, a precursor to
Kristallnacht ( ) or the Night of Broken Glass, also called the November pogrom(s) (, ), was a pogrom against Jews carried out by the Nazi Party's (SA) and (SS) paramilitary forces along with some participation from the Hitler Youth and German civilia ...
. He was imprisoned in
Sachsenhausen concentration camp Sachsenhausen () or Sachsenhausen-Oranienburg was a German Nazi concentration camp in Oranienburg, Germany, used from 1936 until April 1945, shortly before the defeat of Nazi Germany in May later that year. It mainly held political prisoners t ...
for two months and released on the condition that he leave Germany. He was forced to emigrate without his family in October 1938, bound for Cuba. At age 15 in 1939 Arno along with his mother and younger siblings, already on a waiting list for a visa to enter US, obtained a landing permit to join his father in Cuba. With more than 900 other Jewish refugees, the family embarked on the ship the MS ''St. Louis'' from Hamburg to Havana, Along with most other passengers, the Motulskys’ permit to enter Cuba was fraudulently sold by corrupt officials, and Cuba did not allow the refugees to disembark. The captain then asked to land in a US port with the refugees, but the US government refused them entry, as did Canada and other Western Hemisphere nations. The St. Louis was forced to head back towards Germany. A few days before the ship was to land again in Hamburg, four countries agreed to take the refugees. By lots, the passengers were divided among England, France, Belgium, and Netherlands. Arno's family was sent to Belgium in June 1939. The Germans invaded Belgium on May 10, 1940, and 16-year-old Arno was arrested by the Belgians for being a German ‘‘enemy alien.’’ He was separated from his family and spent a year in various internment camps at
Saint-Cyprien, Pyrénées-Orientales Saint-Cyprien (; ) is a Communes of France, commune in the Pyrénées-Orientales Departments of France, department in southern France. Geography History In the 20th century Saint-Cyprien was the site of a camp housing some 70,000 Republican ...
and
Gurs Gurs () in the Pyrénées-Atlantiques department in south-western France. History Gurs was the site of the Gurs internment camp. Nothing remains of the camp; after World War II, a forest was planted on the site where it stood. Geography Gurs ...
in southwestern
France France, officially the French Republic, is a country located primarily in Western Europe. Overseas France, Its overseas regions and territories include French Guiana in South America, Saint Pierre and Miquelon in the Atlantic Ocean#North Atlan ...
. Days before his 18th birthday, he was able to arrange to leave France in June 1941 bearing an American visa. He disembarked from Lisbon for the United States, where he arrived in August 1941 and reunited with his father in
Chicago Chicago is the List of municipalities in Illinois, most populous city in the U.S. state of Illinois and in the Midwestern United States. With a population of 2,746,388, as of the 2020 United States census, 2020 census, it is the List of Unite ...
. Two years later, Motulsky and his father learned that the remainder of their immediate family were in Switzerland, unharmed. The family was reunited in Chicago in 1946, and changed their surname to Molton: only Arno retained the original family name. Motulsky met Gretel Stern (born in 1924, also from Germany) in 1943. They married in 1945.


Education

Motulsky had been barred from his primary education in Germany in 1938 due to his Jewish ancestry, and only attended a year of high school in Belgium before the German invasion, but he maintained his studies during his internment and was able to pass high school equivalency tests in America in 1942. Over the next 2 years, he was able to obtain college qualifications by attending classes at night and on Saturdays while working during the week. He was accepted to medical school at the University of Illinois at Chicago in 1943, but was drafted by the U.S. Army. He attended
Yale University Yale University is a Private university, private Ivy League research university in New Haven, Connecticut, United States. Founded in 1701, Yale is the List of Colonial Colleges, third-oldest institution of higher education in the United Stat ...
as part of the U.S. Army accelerated program, where he attended a genetics course taught by Donald Poulson and "was hooked forever". Motulsky briefly served as an orderly at an army hospital before enrolling in medical school at the
University of Illinois, Chicago The University of Illinois Chicago (UIC) is a public research university in Chicago, Illinois, United States. Its campus is in the Near West Side community area, adjacent to the Chicago Loop. The second campus established under the Universi ...
. He earned his
medical doctorate A Doctor of Medicine (abbreviated MD, from the Latin ) is a medical degree, the meaning of which varies between different jurisdictions. In the United States, and some other countries, the ''MD'' denotes a professional degree of physician. This ge ...
in 3 years, in 1947. Motulsky subsequently completed his
residency Residency may refer to: * Artist-in-residence, a program to sponsor the residence and work of visual artists, writers, musicians, etc. * Concert residency, a series of concerts performed at one venue * Domicile (law), the act of establishing or m ...
in medicine and
fellowship A fellow is a title and form of address for distinguished, learned, or skilled individuals in academia, medicine, research, and industry. The exact meaning of the term differs in each field. In learned or professional societies, the term refers ...
in
hematology Hematology (American and British English spelling differences#ae and oe, spelled haematology in British English) is the branch of medicine concerned with the study of the cause, prognosis, treatment, and prevention of diseases related to bloo ...
at the University of Illinois.


Career

Motulsky's first research efforts were conducted under the supervision of Karl Singer at the
Michael Reese Hospital Michael Reese Hospital and Medical Center was an American hospital located in the Bronzeville neighborhood of Chicago, Illinois. Founded in 1881, Michael Reese Hospital was a major research and teaching hospital and one of the oldest and largest ...
, where he investigated hemoglobinopathies. Subsequent work involved inherited blood disorders, which he conducted at Walter Reed Army Medical Center 1951 to 1953 during service in the U.S. Army. In 1953, Motulsky joined the faculty of the department of medicine at the
University of Washington School of Medicine The University of Washington School of Medicine is the medical school of the University of Washington, a public research university in Seattle, Washington. According to ''U.S. News & World Report''s 2022 Best Graduate School rankings, University ...
, where he continued his work on hemoglobiopathies, developing the first techniques for
hemoglobin electrophoresis Hemoglobin electrophoresis is a blood test that can detect different types of hemoglobin. The test can detect hemoglobin S, the form associated with sickle cell disease, as well as other abnormal types of hemoglobin, such as hemoglobin C. It can ...
. At the request of the chair of the department, Motulsky established the Division of Medical Genetics in 1957. Recruited by Motulsky that same year, Stanley Gartler became the first person to join the division. Motulsky's work spanned multiple subject areas he believed would benefit from genetic investigation. Among others, his professional interests were diverse and included studying the genetics of human blood and serum groups, biochemical genetics, the genetics of
Werner syndrome Werner syndrome (WS) or Werner's syndrome, also known as "adult progeria",James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Dermatology''. (10th ed.). Saunders. . is a rare autosomal recessive disord ...
,
Mendelian Mendelian inheritance (also known as Mendelism) is a type of biological inheritance following the principles originally proposed by Gregor Mendel in 1865 and 1866, re-discovered in 1900 by Hugo de Vries and Carl Correns, and later popularized ...
and
cytogenetic Cytogenetics is essentially a branch of genetics, but is also a part of cell biology/cytology (a subdivision of human anatomy), that is concerned with how the chromosomes relate to cell behaviour, particularly to their behaviour during mitosis an ...
causes of birth defects, ecogenetics, multifactorial diseases, the genetics of
glucose-6-phosphate dehydrogenase deficiency Glucose-6-phosphate dehydrogenase deficiency (G6PDD), also known as favism, is the most common enzyme deficiency anemia worldwide. It is an inborn error of metabolism that predisposes to red blood cell breakdown. Most of the time, those who ar ...
, genetic variation in color vision, genetic variation as a risk factor in anesthesia, and the genetics of pesticide metabolism. In 1957, Motulsky demonstrated that the differential response seen in drug-induced prolonged
apnea Apnea (also spelled apnoea in British English) is the temporary cessation of breathing. During apnea, there is no movement of the muscles of inhalation, and the volume of the lungs initially remains unchanged. Depending on how blocked the ...
during
suxamethonium Suxamethonium chloride (brand names Scoline and Sucostrin, among others), also known as suxamethonium or succinylcholine, or simply sux in medical abbreviation, is a medication used to cause short-term paralysis as part of general anesthesia. T ...
anesthesia could be attributed to a
pseudocholinesterase deficiency Pseudocholinesterase deficiency is an autosomal recessive inherited blood plasma enzyme abnormality in which the body's production of butyrylcholinesterase (BCHE; pseudocholinesterase aka PCE) is impaired. People who have this abnormality may be ...
genoytpe. This discovery led him to propose the concept of
pharmacogenetics Pharmacogenomics, often abbreviated "PGx," is the study of the role of the genome in drug response. Its name ('' pharmaco-'' + ''genomics'') reflects its combining of pharmacology and genomics. Pharmacogenomics analyzes how the genetic makeup o ...
in 1964. Motulsky was the first to propose that bone marrow transplantation could be used to cure genetic disorders of the hematopoietic system, which his group was the first to practically demonstrate by using transplantation to cure
hereditary spherocytosis Hereditary spherocytosis (HS) is a congenital hemolytic disorder wherein a genetic genetic mutation, mutation coding for a structural membrane protein phenotype causes the red blood cells to be sphere-shaped (spherocytosis), rather than the norma ...
in a murine model in 1967. Starting in 1970, Motulsky mentored his trainee
Joseph L. Goldstein Joseph Leonard Goldstein ForMemRS (born April 18, 1940) is an American biochemist. He received the Nobel Prize in Physiology or Medicine in 1985, along with fellow University of Texas Southwestern researcher, Michael Brown, for their studies r ...
in investigations of the genetic variability of lipid metabolism. This collaboration led to discovery of the familial inheritance patterns of
hyperlipidemia Hyperlipidemia is abnormally high levels of any or all lipids (e.g. fats, triglycerides, cholesterol, phospholipids) or lipoproteins in the blood. citing: and The term ''hyperlipidemia'' refers to the laboratory finding itself and is also use ...
, and provided the first evidence that familial hypercholesterolemia was a monogenic disorder. These were also foundational studies for Goldstein's 1985
Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine () is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, acco ...
awarded with Michael Brown, “for their discoveries concerning the regulation of cholesterol metabolism.” During the 1980's Motulsky collaborated with colleague Samir Deeb to investigate the genetics underlying
color vision Color vision, a feature of visual perception, is an ability to perceive differences between light composed of different frequencies independently of light intensity. Color perception is a part of the larger visual system and is mediated by a co ...
, eventually identifying common
genetic polymorphisms A gene is said to be polymorphic if more than one allele occupies that gene's locus within a population. In addition to having more than one allele at a specific locus, each allele must also occur in the population at a rate of at least 1% to ge ...
and
structural variants Genomic structural variation is the variation in structure of an organism's chromosome, such as deletions, duplications, copy-number variants, insertions, inversions and translocations. Originally, a structure variation affects a sequence length ab ...
that influence color perception. During the course of his career, Motulsky mentored many postdoctoral trainees in medical genetics, including Robert Sparks, John Mulvihill, Philip J. Fialkow, Charles Epstein, Frederick Hecht, David E. Comings,
Judith Goslin Hall Judith Goslin Hall (born July 3, 1939) is a pediatrician, clinical geneticist and dysmorphologist who is a dual citizen of the United States and Canada. Early life and education The daughter of a minister, Judith Goslin Hall was born on Jul ...
, Gilbert S. Omenn,
George Stamatoyannopoulos George Stamatoyannopoulos (; 11 March 1934 – 16 June 2018) was a Greek geneticist who taught at the University of Washington. Born in Athens on 11 March 1934, Stamatoyannopoulos earned a medical degree and doctorate from the University of Athen ...
, George Fraser, Wylie Burke, Ephrat Levy-Lahad, and
Joseph L. Goldstein Joseph Leonard Goldstein ForMemRS (born April 18, 1940) is an American biochemist. He received the Nobel Prize in Physiology or Medicine in 1985, along with fellow University of Texas Southwestern researcher, Michael Brown, for their studies r ...
. Many of these trainees went on to establish genetics programs at a number of medical schools.


Legacy

When he was 19, Motulsky wrote a short memoir (in English) of his experiences from 1939 to 1941, and this was published after his death. He also discussed his experiences in a -hour interview with the
USC Shoah Foundation The USC Shoah Foundation – The Institute for Visual History and Education, formerly Survivors of the Shoah Visual History Foundation, is a nonprofit organization dedicated to making audio-visual interviews with survivors and witnesses of the ...
, as well as a series of interviews with
Deutschlandradio Deutschlandradio (DLR; ) is a national German public radio broadcaster. History ''Deutschlandfunk'' was originally a West German news radio targeting listeners within West Germany as well as in neighbouring countries, ''Deutschlandfunk Kultur'' ...
. In 2012, Motulsky was honored in a ceremony by the
US State Department The United States Department of State (DOS), or simply the State Department, is an executive department of the U.S. federal government responsible for the country's foreign policy and relations. Equivalent to the ministry of foreign affairs o ...
for the survivors of the MS St. Louis and diplomats from countries that accepted them as refugees. He co-wrote his final publication, his autobiography, with
Mary-Claire King Mary-Claire King (born February 27, 1946) is an American geneticist. She was the first to show that breast cancer can be inherited due to mutations in the gene she called ''BRCA1''. She studies human genetics and is particularly interested in g ...
. Much of this memoir was based on an interview done as part of the Conversations in Genetics series. Obituaries were published in the New York Times, American Journal of Human Genetics, American Journal of Medical Genetics, Genetics in Medicine, the Journal of Clinical investigation, the Lancet, the Scientist, the Pharmacologist, the British Journal of Medicine, the National Academy of Sciences, and UW Medicine. He was inducted as a member into the
National Academy of Medicine The National Academy of Medicine (NAM), known as the Institute of Medicine (IoM) until 2015, is an American nonprofit, non-governmental organization. The National Academy of Medicine is a part of the National Academies of Sciences, Engineerin ...
, the
National Academy of Sciences The National Academy of Sciences (NAS) is a United States nonprofit, NGO, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the ...
and the
American Philosophical Society The American Philosophical Society (APS) is an American scholarly organization and learned society founded in 1743 in Philadelphia that promotes knowledge in the humanities and natural sciences through research, professional meetings, publicat ...
.


References


External links

* {{DEFAULTSORT:Motulsky, Arno 1923 births 2018 deaths American geneticists American Journal of Human Genetics editors Gurs internment camp survivors Jewish emigrants from Nazi Germany to the United States Medical geneticists Members of the American Philosophical Society Members of the National Academy of Medicine Members of the United States National Academy of Sciences People from East Prussia People from Primorsk, Kaliningrad Oblast University of Illinois Chicago alumni Yale University alumni